Bone morphogenetic proteins (BMPs) are members of the TGF-β superfamily, and some studies demonstrated that BMPs enhance tumorigenesis and metastasis. The purpose of this study was to identify whether BMP-2 levels are elevated in the serum of non-small-cell lung cancer (NSCLC) patients and are associated with the stage and overall survival. Blood samples from 150 patients with NSCLC were analyzed. Also, 69 healthy volunteers were tested as control group. In NSCLC patients, whole blood was obtained before beginning any treatment modalities, and serum BMP-2 levels were quantified by commercially available ELISA kit. The NSCLC group demonstrated a significantly higher level of serum BMP-2 than the control group. (The median levels were 25.50 pg/ml for the control group and 72.23 pg/ml for the NSCLC group, P < 0.001). The median serum BMP-2 level in the advanced stage group (stage IIIb or IV) was significantly more elevated than that of the localized stage group (stage I, II, IIIa) (75.66 pg/ml and 44.36 pg/ml, P = 0.006). Patients with multiple metastatic sites (≥5) showed significantly higher level of serum BMP-2 than the patients with less than 5 metastatic sites. (79.39 pg/ml vs. 59.70 pg/ml, P = 0.013), and the median serum BMP-2 level from the patients with multiple metastatic organs (≥3) was significantly higher than that from the patients with single or two metastatic organs (<2) (89.39 pg/ml vs. 66.90 pg/ml, P = 0.001). Moreover, the patients with relatively lower BMP-2 level (≤70 pg/ml) had longer median overall survival than the patients with higher BMP-2 level (>70 pg/ml). (525 days vs. 260 days). One-year survival rate for the patients with lower BMP-2 level was also higher than that for the patients with higher BMP-2 level. (59.6% versus 40.2%, P = 0.034). The serum BMP-2 level is positively correlated with the stage and metastatic burden and maybe a probable predictor of survival in the NSCLC patients.